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Glioblastoma: Overcoming fundamental biological and delivery barriers to therapy
Genaro R Villa1,2,3, Ashish D Patel2,4,5, David A Reardon2,4
1Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Mass General Brigham, Boston, MA, USA.
Abstract:
Glioblastoma remains the most aggressive primary malignant brain tumor in adults, with survival largely unchanged despite advances in molecular diagnostics and supportive care. Therapeutic failure reflects fundamental biological and anatomical barriers, including intratumoral heterogeneity, an immunosuppressive tumor microenvironment, and restricted drug delivery across the blood-brain barrier. In this Review, we summarize the current standard of care and critically examine emerging strategies aimed at overcoming these constraints, including locoregional delivery technologies, immunotherapy, biomarker-defined precision approaches, and adaptive clinical trial designs. We highlight key translational and clinical studies shaping the field and discuss principles for developing more effective, integrated therapeutic paradigms.
Insights
Glioblastoma treatment faces challenges due to tumor complexity and drug delivery limits. Emerging strategies like immunotherapy and precision medicine offer new hope for improving survival in adult brain tumor patients.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Translational Medicine
Background:
- Glioblastoma is the most aggressive adult primary malignant brain tumor.
- Survival rates have not significantly improved despite diagnostic and supportive care advancements.
- Therapeutic failure is linked to intratumoral heterogeneity, an immunosuppressive tumor microenvironment, and poor drug delivery across the blood-brain barrier.
Purpose of the Study:
- To review the current standard of care for glioblastoma.
- To critically examine emerging therapeutic strategies for glioblastoma.
- To discuss principles for developing integrated therapeutic paradigms for glioblastoma.
Main Methods:
- Review of current standard of care.
- Examination of emerging strategies including locoregional delivery, immunotherapy, precision approaches, and adaptive trial designs.
- Highlighting key translational and clinical studies.
Main Results:
- Glioblastoma presents significant biological and anatomical barriers to treatment.
- Emerging strategies aim to overcome intratumoral heterogeneity, immunosuppression, and drug delivery issues.
- Key studies are shaping the development of new therapeutic paradigms.
Conclusions:
- Despite challenges, advancements in diagnostics and supportive care have not substantially improved glioblastoma survival.
- Innovative approaches focusing on overcoming tumor-specific barriers are crucial.
- Integrated therapeutic strategies are essential for developing more effective glioblastoma treatments.
